IT IS lunch time at the University of Hawaii in Honolulu, and Ryuzo
Yanagimachi is encouraging a visiting reporter to eat his own words. 鈥淭his year,
a magazine predicted who was likely to clone the next adult animal,鈥� he says.
鈥淵ou know, my lab didn鈥檛 even make that list.鈥�
True, the article to which he refers
(鈥淐lone Watching鈥�, 麻豆传媒, 9 May, p 35)
gave no clue that Yanagimachi and his colleagues
would, within two months, unveil dozens of cloned mice. But New
Scientist wasn鈥檛 alone in overlooking the potential of this Hawaiian
lab鈥攊nitially, even Yanagimachi wasn鈥檛 let into the secret.
To understand the background to the scientific coup of the year, it helps to
visit Yanagimachi鈥檚 base. On a campus where offices with a view of the
forbidding volcanic walls of Diamond Head Crater must be highly coveted,
Yanagimachi has for decades inhabited a windowless suite.
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If he is oblivious to his surroundings, it is because he is so focused on his
science, says Tony Perry, a researcher in his lab. It isn鈥檛 unusual for
Yanagimachi, now 70, to work 12 hours a day, seven days a week. 鈥淗e works hard,
knows everything, and is incredibly supportive,鈥� says Perry.
Yanagimachi was best known for his work on IVF in animals. But when Dolly the
sheep made her debut, Teruhito Wakayama, one of Yanagimachi鈥檚 postdocs, seized
his chance to work on an idea that had fascinated him since reading science
fiction as a boy in Japan. 鈥淚 used to dream about cloning,鈥� he says.
Everyone working for Yanagimachi has to work three days a week on their main
project, but can explore other interests in the remaining time. Wakayama鈥檚 main
challenge was to create mice from freeze-dried sperm. Cloning became his
hobby.
At first, he said little to Yanagimachi. Cloning an adult animal involves
reprogramming the genes from one of its cells. Mice were thought to be difficult
because their genes become active early on in embryonic development, giving
little time to achieve the necessary reprogramming.
Without time for elaborate preparations, Wakayama used the materials at hand.
For his donor cells, he used the cumulus cells which coat the surface of the
egg. He was used to injecting sperm heads into eggs. So rather than fusing donor
cells with eggs stripped of their chromosomes, like other groups, he injected
only the nuclei of the donor cells.
Wakayama implanted the resulting embryos in surrogate mothers. Yanagimachi
first found out about the project in August 1997, when Wakayama dragged him to a
microscope. 鈥淚 saw a healthy mouse fetus with a beating heart,鈥� Yanagimachi
remembers. The lab鈥檚 focus shifted overnight. The fruit of their labour came on
3 October 1997 when Cumulina, the first cloned mouse, was born.
Wakayama鈥檚 original choice of cells turned out to be a lucky break. About 2
per cent of cumulus cells yielded clones, while the researchers were unable to
produce full-term embryos from Sertoli cells, which nourish developing sperm,
and neurons. The team has since produced more than 80 cloned mice鈥攕ome of
them clones of clones of clones of clones.
This is the most important breakthrough in cloning since Ian Wilmut鈥檚 team at
the Roslin Institute near Edinburgh produced Dolly. But until Cumulina鈥檚
arrival, the prospects for ever again cloning another adult animal had seemed
remote. In January, Norton Zinder of Rockefeller University in New York spoke
for many when he speculated that Dolly was cloned from a contaminating fetal
cell, rather than adult tissue.
Those dark days of doubt now seem like a distant memory. Researchers in Japan
and New Zealand both claim to have cloned adult cows and a genetic analysis
appears to confirm that Dolly was cloned from an adult.
Investors are keenly aware of the progress being made, says Simon Best, chief
executive of Roslin Biomed, a company set up to develop biomedical applications
from Wilmut鈥檚 work. 鈥淓ach time a new group clones an animal, I predict they鈥檒l
be able to set up a company the next day,鈥� he says. Not surprisingly,
researchers are beginning to clash over patent rights to cloning technology.
One exciting area would be to combine cloning with another of the big
biological announcements of 1998, the isolation of human embryonic stem cells.
Adult cells would be cloned to create an embryo, from which stem cells could be
extracted to grow tissues for transplants. And as 麻豆传媒
revealed in July, this need not involve the creation of a viable human embryo,
if the egg cells used in the cloning process were from cows.
Cumulina鈥檚 other legacy will be a boon for basic science. Because so much is
already known about mouse genes and because mice reproduce so quickly, the
Hawaiian researchers could rapidly address some puzzling questions. When animals
are cloned from adult cells, do they age more rapidly? Why is the success rate
of cloning still so low? How do long dormant genes get revived during cloning?
Yanagimachi should have some answers next year.
